The objectives of this research project are to provide a better understanding of the genetically determined factors which influence the immunogenicity of alloantigens present on transplanted tissue, and to learn more about the genetics of the cell surface antigens themselves. As a model system we will use the Thymus cell antigen-1 (Thy-1) cell surface antigens of the mouse. We have shown that the immunogenicity of these antigens is strongly affected by donor genes and that specific antibody responses against Thy-1 can be quantitated by means of a complement-dependent cytolytic plaque assay. Because the genes which confer augmented immunogenicity upon Thy-1 antigens are expressed in a dominant or codominant manner, Fl hybrids between highly immunogenic and poorly immunogenic inbred strains show elevated Thy-1 immunogenicity. By backcrossing such hybrids to the poorly immunogenic strain we will estimate the number of augmenting of "helper" loci. The segregation patterns of these loci will be compared with those of coat color genes and biochemical polymorphisms in an attempt to define their chromosomal locations. Serial backcrossing of the hybrids to the poorly immunogenic parental strain should allow separation of the individual "helper" genes so that their relative strengths can be compared and their abilities to augment immune response against both of the known Thy-1 antigenic variants can be assessed. In a separate set of serial backcrosses we will attempt to "breed out" any putative helper genes and therefore to ascertain whether antibody responses to Thy-1 are totally dependent upon the presence of these genes. The last experiment of this type will examine the question of whether the H-Y minor histocompatibility antigen can act as a "helper" determinant, thereby enhancing the immunogenicity of associated Thy-1 molecules. In the second part of the project we will use a backcross design to define more precisely the position of the Thy-1 antigen-determining locus (Thy-1) on Chromosome 9 and of the major histocompatibility complex (H-2) on Chromosome 17. This information will be used in testing for the possible presence of helper genes in or near the Thy-1 or H-2 chromosomal regions.